Fabry keratopathy: manifestations and changes over time.

AIMS: The goal was to find if changes in Fabry keratopathy were clinically observable over time. Also observed were variations of Fabry keratopathy, supplemental features, unique presentations and differences between keratopathies of right and left corneas and the same family and genotype. METHODS: Biomicroscopic images of Fabry keratopathy in 10 persons with classic Fabry disease, 5 men and 5 women, were captured over an 18-month period. The keratopathies were categorised and scrutinised for changes over time, and differences between corneas of the same individual, family and genotype. RESULTS: Fabry keratopathy ranged from mild change to marked change over 18 months. There was a great variety of whorl patterns. A few keratopathies were amorphous without vortices and many vortices were supplemented with amorphous features. All keratopathies were accompanied by diffuse epithelial haze. There was a range from negligible difference to marked difference between right and left eyes of the same individuals with similarities appearing as imprecise mirror images of each other. In some corneas, prominent vertical streams from the superior limbus integrated into the primary keratopathy. Comparisons between persons with the same family and genotype were obscured by gender and differences between right and left eyes. CONCLUSIONS: Practitioners should be better able to detect Fabry disease having a fuller understanding of the variety of presentations of the dynamic, pathognomonic Fabry keratopathy. Routes of continuous centripetal renewal of corneal epithelium are spatially unique to each eye, in some cases subsidised by direct contribution of basal cells streamed from the superior limbus.

Conjunctival lymphangiectasia associated with classic Fabry disease.

BACKGROUND: Fabry disease (FD) is a treatable multisystem disease caused by a defect in the alpha-galactosidase gene. Ocular signs of FD, including corneal verticillata, are among the earliest diagnostic findings. Conjunctival lymphangiectasia (CL) has not previously been associated with FD. METHODS: We examined the eyes of a cohort of 13 adult patients, eight men and five women, with documented classic FD, all treated with enzyme replacement therapy (ERT) at the University of Alabama at Birmingham between February 2014 and April 2015. The average age was 48 years with a range of 35-55 years for men and 21-71 years for women. The mean duration of ERT was 8.4 years (men 8.9 years, women 7.6 years) with a range of 4-14 years. Classical Fabry mutations included Q283X, R227X, W236X and W277X. A high resolution Haag-Streit BQ-900 slit lamp with EyeCap imaging system was used to record conjunctival images. RESULTS: CL was observed in 11 of the 13 patients (85%) despite long-term ERT. Clinical presentations included single cysts, beaded dilatations and areas of conjunctival oedema. Lesions were located within 6 mm of the corneal limbus. Ten of the 13 subjects (77%) had Fabry-related cataracts and all 13 demonstrated bilateral corneal verticillata. Twelve of the 13 patients had evidence of dry eye, 9 of whom were symptomatic, and 10 had peripheral lymphoedema. CONCLUSION: CL represents a common but under-recognised ocular manifestation of FD, which persists despite ERT, and is often accompanied by peripheral lymphoedema and dry eye syndrome.

Fabry disease: a review of ophthalmic and systemic manifestations.

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by accumulation of Gb-3 (globotriaosylceramide) in cellular lysosomes of tissues throughout the body. With advancing age, lysosomal Gb-3 accumulates in blood vessel walls, nerve cells, smooth muscle, and vital organs. Premature death commonly results from renal failure, heart attack, and stroke when the diagnosis is delayed or overlooked. One of the earliest and most distinctive physical features of FD is a whorl-like keratopathy. This finding is easily identifiable during a routine eye examination with a slit lamp, making eye care practitioners uniquely postured to identify patients and families with this incurable genetic disorder. Much of the pain, suffering, and adverse impact of FD can be avoided if an alert eye care expert sees the patient at an early age, identifies the condition, and makes the appropriate referral. The importance of obtaining a thorough medical history, ancestral health history, and review of systems to correlate ocular and systemic manifestations is emphasized. This report reviews the multisystem involvement of FD and describes the clinical characteristics and expected chronological appearance of ophthalmic and systemic manifestations. The discoveries of late-onset variants, increased prevalence, and modified inheritance pattern of FD are discussed. The profound therapeutic effects of recombinant enzyme replacement therapy (ERT) on multiple organ systems are detailed and demonstrated in a Fabry proband. Improved quality and quantity of life after initiation of ERT underscore the importance of early recognition and correlation of FD symptoms and clinical signs. Treatment strategies and the effectiveness of new adjunctive chaperone therapy are addressed.